title: A mutation in the leptin receptor  is associated with Entamoeba histolytica  infection in children.
abstract: Malnutrition substantially increases susceptibility to Entamoeba histolytica in children. Leptin is a hormone produced by adipocytes that inhibits food intake, influences the immune system, and is suppressed in malnourished children. Therefore we hypothesized that diminished leptin function may increase susceptibility to E. histolytica infection. We prospectively observed a cohort of children, beginning at preschool age, for infection by the parasite E. histolytica every other day over 9 years and evaluated them for genetic variants in leptin (LEP) and the leptin receptor (LEPR). We found increased susceptibility to intestinal infection by this parasite associated with an amino acid substitution in the cytokine receptor homology domain 1 of LEPR. Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared with those homozygous for the ancestral glutamine allele (223Q). An association of this allele with amebic liver abscess was also determined in an independent cohort of adult patients. In addition, mice carrying at least 1 copy of the R allele of Lepr were more susceptible to infection and exhibited greater levels of mucosal destruction and intestinal epithelial apoptosis after amebic infection. These findings suggest that leptin signaling is important in mucosal defense against amebiasis and that polymorphisms in the leptin receptor explain differences in susceptibility of children in the Bangladesh cohort to amebiasis.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. pduggal@jhsph.edu
authors.forename: Priya
authors.initials: P
authors.lastname: Duggal
authors.forename: Xiaoti
authors.initials: X
authors.lastname: Guo
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Peterson
authors.forename: Stacy
authors.initials: S
authors.lastname: Ricklefs
authors.forename: Dinesh
authors.initials: D
authors.lastname: Mondal
authors.forename: Faisal
authors.initials: F
authors.lastname: Alam
authors.forename: Zannatun
authors.initials: Z
authors.lastname: Noor
authors.forename: Hans P
authors.initials: HP
authors.lastname: Verkerke
authors.forename: Chelsea
authors.initials: C
authors.lastname: Marie
authors.forename: Charles A
authors.initials: CA
authors.lastname: Leduc
authors.forename: Streamson C
authors.initials: SC
authors.lastname: Chua
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Leibel
authors.forename: Eric
authors.initials: E
authors.lastname: Houpt
authors.forename: Carol A
authors.initials: CA
authors.lastname: Gilchrist
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.forename: William A
authors.initials: WA
authors.lastname: Petri
mesh_terms: D000483:Alleles; D017209:Apoptosis; D002675:Child, Preschool; D015331:Cohort Studies; D004748:Entamoeba histolytica / Q000378:metabolism*; D004749:Entamoebiasis / Q000235:genetics* / Q000469:parasitology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008100:Liver Abscess / Q000378:metabolism; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D054411:Receptors, Leptin / Q000235:genetics*
chemical_list: D054411:Receptors, Leptin; D005973:Glutamine